1. Field of the Invention
This invention relates to an oil-in-water emulsion formulation containing hydroquinone and retinol. More specifically this invention relates to oil-in-water emulsions that contain hydroquinone entrapped in micro-agglomerates and/or impregnated in porous microparticles and in free form; and retinol-impregnated porous microparticles.
2. Background to the Invention
Hydroquinone is a reduced quinone, well-recognized as an efficacious skin-lightening agent. When topically applied, it produces a reversible depigmentation of the skin by inhibiting the enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylalanine, as well as suppressing other metabolic processes of melanocytes. In a clinical setting, hydroquinone is employed to treat hypermelanosis. It has likewise been utilized to bleach hyperpigmented skin conditions including chloasma, melasma, freckles, and senile lentigines. Hydroquinone is available in over-the-counter and prescription products. Although hydroquinone is considered a mild irritant, it displays minimal toxicity in humans.
Retinol, along with other retinoids, has enjoyed increasing popularity as an active ingredient in skin care compositions, especially for photoaging and sun damage. However, more so than other retinoids, retinol tends to decompose on exposure to light, heat, and oxygen. The problem of decomposition has been addressed to some extent by formulating retinol with antioxidants and chelating agents, and storing it in opaque or colored containers, and several patents and published applications, for example, PCT International Application Publication No. WO 93/00085 and European Patent Application Publication Nos. 0 440 398 and 0 596 106, all to Johnson & Johnson, describe water-in-oil emulsions containing retinol, which are asserted to be stable. U.S. Pat. No. 5,891,740 to Rinaldi et al. discloses soft capsule fill formulations containing retinol. The fill material for the '740 patent may be optionally thickened with silicone oil, or may be an emulsion comprising a silicon oil. Ascorbic acid may be present as ascorbic acid-impregnated microparticles and or within the emulsion. This patent makes no disclosure nor suggestion of hydroquinone in separate microparticles or micro-agglomerates, and no disclosure of an oil-in-water emulsion containing them together with retinol-impregnated microparticles.
U.S. Pat. No. 5,851,538, discloses an oil-in-water emulsion containing retinol. Further, this reference discloses oil-in-water emulsions containing the retinoids in microporous microspheres. Retinol and melanin are impregnated one after the other into the same microspheres and then the microspheres are used in the oil-in-water emulsion. There is no disclosure nor suggestion in the '538 patent of hydroquinone in separate microparticles or micro-agglomerates, and no disclosure of an oil-in-water emulsion containing them together with retinol-impregnated microparticles. Most importantly, this reference makes no suggestion of having some free hydroquinone in the emulsion to keep the loaded hydroquinone from coming out of the porous carriers and provide some immediate therapeutic benefit. Lastly, the inclusion of some small level of free hydroquinone reduces the “powder load” on the final emulsion and thereby produces an improved product.
The disclosures of these and other documents referred to in this application are incorporated herein by reference.
It would be of value to have a stable oil-in-water emulsion formulation containing both hydroquinone and retinol as dermatologists are constantly searching for improved formulations that provide a desired therapeutic effect.